Renin-angiotensin system contributes to naive T-cell migration in vivo.

Angiotensin II (Ang II) plays an important role in the regulation of the T-cell response during inflammation. However, the cellular mechanisms underlying the regulation of lymphocytes under physiologic conditions have not yet been studied. Here, we tested the influence of Ang II on T-cell migration using T cells from BALB/c mice. The results obtained in vivo showed that when Ang II production or the AT1 receptor were blocked, T-cell counts were enhanced in blood but decreased in the spleen. The significance of these effects was confirmed by observing that these cells migrate, through fibronectin to Ang II via the AT1 receptor. We also observed a gradient of Ang II from peripheral blood to the spleen, which explains its chemotactic effect on this organ. The following cellular mechanisms were identified to mediate the Ang II effect: upregulation of the chemokine receptor CCR9; upregulation of the adhesion molecule CD62L; increased production of the chemokines CCL19 and CCL25 in the spleen. These results indicate that the higher levels of Ang II in the spleen and AT1 receptor activation contribute to migration of naive T cells to the spleen, which expands our understanding on how the Ang II/AT1 receptor axis contributes to adaptive immunity.

Computed tomography changes diagnosis, management and surgical planning of ankle fractures.

PURPOSE: To demonstrate how the use of adjunctive Computed Tomography (CT) can modify diagnosis, treatment options, and operative planning of ankle fractures in comparison with conventional radiographs (CR) in isolation. MATERIALS AND METHODS: A total of 53 patients diagnosed with an ankle fracture between 2011 and 2016, were assessed with CT and CR. Evaluations of the fractures using CR in isolation and CR combined with CT were compared using different readers. Fractures were assessed in terms of type, displacement, size, associated injuries, treatment, patient position and surgical planning. RESULTS: The medial malleolus fractures characteristics (posteromedial fragment and anterior colliculus), the presence of posterior malleolus fracture and its characteristics (displacement, size, posteromedial or posterolateral segment) (ps < 0.042), syndesmosis injury (p < 0.001), and the absence of deltoid ligament lesion (p < 0.001), were more evident with the combination of CT and radiographs. There was an increase in operative indication (p = 0.007), prone positioning (p = 0.002), posterior malleolus surgical treatment (p < 0.001), posterolateral approach for the lateral malleolus (p = 0.003), and syndesmosis fixation (p = 0.020) with the association of CT and CR, among all groups of expertise, with a high interobserver reliability (> 0.75). CONCLUSIONS: The CR may fail to demonstrate subtle lesions, such as posterior malleolus fractures and syndesmotic injuries. The CT evaluation increases the diagnostic precision and improves the quality of information the surgeon receives, what might positively affect patient care. LEVEL OF EVIDENCE III: Retrospective Comparative Study.

Unravelling soybean responses to early and late Tetranychus urticae (Acari: Tetranychidae) infestation.

Soybean is a crucial source of food, protein, and oil worldwide that is facing challenges from biotic stresses. Infestation of Tetranychus urticae Koch (Acari: Tetranychidae) stands out as detrimentally affecting plant growth and grain production. Understanding soybean responses to T. urticae infestation is pivotal for unravelling the dynamics of mite-plant interactions. We evaluated the physiological and molecular responses of soybean plants to mite infestation after 5 and 21 days. We employed visual/microscopy observations of leaf damage, H2O2 accumulation, and lipid peroxidation. Additionally, the impact of mite infestation on shoot length/dry weight, chlorophyll concentration, and development stages was analysed. Proteomic analysis identified differentially abundant proteins (DAPs) after early (5 days) and late (21 days) infestation. Furthermore, GO, KEGG, and protein-protein interaction analyses were performed to understand effects on metabolic pathways. Throughout the analysed period, symptoms of leaf damage, H2O2 accumulation, and lipid peroxidation consistently increased. Mite infestation reduced shoot length/dry weight, chlorophyll concentration, and development stage duration. Proteomics revealed 185 and 266 DAPs after early and late mite infestation, respectively, indicating a complex remodelling of metabolic pathways. Photorespiration, chlorophyll synthesis, amino acid metabolism, and Krebs cycle/energy production were impacted after both early and late infestation. Additionally, specific metabolic pathways were modified only after early or late infestation. This study underscores the detrimental effects of mite infestation on soybean physiology and metabolism. DAPs offer potential in breeding programs for enhanced resistance. Overall, this research highlights the complex nature of soybean response to mite infestation, providing insights for intervention and breeding strategies.

Characterization of ecto-ATPase activity in the surface of LLC-PK1 cells and its modulation by ischemic conditions.

BACKGROUND: The concentration of extracellular nucleotides is regulated by enzymes that have their catalytic site facing the extracellular space, the so-called ecto-enzymes. METHODS: We used LLC-PK1 cells, a well-characterized porcine renal proximal tubule cell line, to biochemically characterize ecto-ATPase activity in the luminal surface. The [γ-(32)P]Pi released after reaction was measured in aliquots of the supernatant by liquid scintillation. RESULTS: This activity was linear with time up to 20min of reaction and stimulated by divalent metals. The ecto-ATPase activity measured in the presence of 5mM MgCl(2) was (1) optimum at pH 8, (2) insensitive to different inhibitors of intracellular ATPases, (3) inhibited by 1mM suramin, an inhibitor of ecto-ATPases, (4) sensitive to high concentrations of sodium azide (NaN(3)) and (5) also able to hydrolyze ADP in the extracellular medium. The ATP:ADP hydrolysis ratio calculated was 4:1. The ecto-ADPase activity was also inhibited by suramin and NaN(3). The dose-response of ATP revealed a hyperbolic profile with maximal velocity of 25.2±1.2nmol Pixmg(-1)xmin(-1) and K(0.5) of 0.07±0.01mM. When cells were submitted to ischemia, the E-NTPDase activity was reduced with time, achieving 71% inhibition at 60min of ischemia. CONCLUSION: Our results suggest that the ecto-ATPase activity of LLC-PK1 cells has the characteristics of a type 3 E-NTPDase which is inhibited by ischemia. GENERAL SIGNIFICANCE: This could represent an important pathophysiologic mechanism that explains the increase in ATP concentration in the extracellular milieu in the proximal tubule during ischemia.

Na+-dependent and Na+-independent mechanisms for inorganic phosphate uptake in Trypanosoma rangeli.

BACKGROUND: Trypanosoma rangeli is dependent on the presence of exogenous orthophosphate (Pi) for maximal growth and ecto-phosphatase activity is responsible for Pi supply under low Pi. Here we investigated the mechanisms of Pi uptake. METHODS: We investigated the kinetics of 32Pi transport, its Na+ and H+ dependence, its correlation with the Na+-ATPase and H+-ATPase, and gene expression of the Na+:Pi cotransporter and Na+-ATPase. RESULTS: T. rangeli grown under limiting Pi transports this anion to the cytosol in the absence and presence of Na+, suggesting that influx is mediated by both Na+-independent and Na+-dependent transporters. Cloning studies demonstrated that this parasite expresses a Pi transporter not previously studied in trypanosomatids. The H+ ionophore, carbonylcyanide-p-trifluoromethoxyphenylhydrazone, decreased both components of 32Pi influx by 80-95%. The H+-ATPase inhibitor, bafilomycin A1, inhibited the Na+-independent mechanism. Furosemide, an inhibitor of ouabain-insensitive Na+-ATPase, decreased both uptake mechanisms of 32Pi to the same extent, whereas ouabain had no effect, indicating that the former is the pump responsible for inwardly directed Na+ and the electric gradients required by the transporters. Parasite growth in high Pi had a lower Pi influx than that found in those grown in low Pi, without alteration in TrPho89 expression, showing that turnover of the transporters is stimulated by Pi starvation. CONCLUSIONS: Two modes of Pi transport, one coupled to Na+-ATPase and other coupled to H+-ATPase seem to be responsible for Pi acquisition during development of T. rangeli. GENERAL SIGNIFICANCE: This study provides the first description of the mechanism of Pi transport across the plasma membrane of trypanosomatids.

Protein kinase C-mediated ATP stimulation of Na(+)-ATPase activity in LLC-PK1 cells involves a P2Y2 and/or P2Y4 receptor.

ATP-activated P2Y receptors play an important role in renal sodium excretion. The aim of this study was to evaluate the modulation of ATPase-driven sodium reabsorption in the proximal tubule by ATP or adenosine (Ado). LLC-PK1 cells, a model of porcine proximal tubule cells, were used. ATP (10(-6)M) or Ado (10(-6)M) specifically stimulated Na(+)-ATPase activity without any changes in (Na(+)+K(+))-ATPase activity. Our results show that the Ado effect is mediated by its conversion to ATP. Furthermore, it was observed that the effect of ATP was mimicked by UTP, ATPγS and 2-thio-UTP, an agonist of P2Y2 and P2Y4 receptors. In addition, ATP-stimulated Na(+)-ATPase activity involves protein kinase C (PKC). Our results indicate that ATP-induced stimulation of proximal tubule Na(+)-ATPase activity is mediated by a PKC-dependent P2Y2 and/or P2Y4 pathway. These findings provide new perspectives on the role of the effect of P2Y-mediated extracellular ATP on renal sodium handling.

Myogenic oscillations in rabbit ocular vasculature are very low frequency.

BACKGROUND/AIMS: In a previously described model of isolated rabbit eye, we detected myogenic intrinsic vascular tone of unknown origin in the ophthalmic artery. In order to better understand the origin of these low frequency oscillations, we analyzed their spectral characteristics using fast Fourier. METHODS: Hybrid New Zealand rabbits of either sex (n = 24) were used; they were divided into 2 groups according to age. The spectral characteristics of the myogenic behaviour of the rabbit external ophthalmic artery were analyzed using the fast Fourier algorithm. RESULTS: The frequency of the oscillations of the myogenic activity seen in the rabbit external ophthalmic artery varied between 0.033 and 0.066 Hz (mean 0.045 ± 0.012 Hz), all in the region of very low frequency (VLF) oscillations (VLF <0.07 Hz for the rabbit). The frequency of spontaneous oscillations was higher in younger animals. CONCLUSION: Fast Fourier analysis proved to be an adequate mathematical tool to analyze the myogenic tone oscillations, which were all in the range of VLF in the model we used. These results indicate that myogenic vascular function of ocular blood flow is composed of VLF oscillations, and they provide a new explanation for the origin of VLF in arterial spectra. They also suggest that the ocular local myogenic vascular function observed is more efficient in younger animals.

Opioid-free mastectomy under thoracic epidural anesthesia-analgesia in a patient with critical tracheal stenosis: a case report.

Mastectomy is traditionally performed under general anaesthesia and invasive ventilation, and is often complemented with regional techniques. In this setting, tracheal stenosis can pose a challenge to airway management. The aim of this report is to describe the successful management of a 68-year-old woman with severe subglottic tracheal stenosis undergoing mastectomy due to breast cancer. Surgery was performed without airway instrumentation under an opioid-free regimen consisting of thoracic epidural, propofol and dexmedetomidine perfusion, and non-opioid analgesics. Spontaneous ventilation and adequate perioperative analgesia were achieved. Opioid-free anaesthesia without airway instrumentation, consisting of thoracic epidural anaesthesia and sedation, is a good alternative in patients undergoing mastectomy in whom airway manipulation is best avoided.

Alterations induced by titanium dioxide nanoparticles (nano-TiO2) in fertilization and embryonic and larval development of the tropical sea urchin Lytechinus variegatus.

The release of nanomaterials into the environment is the cause of an emerging concern. Titanium dioxide nanoparticles (nano-TiO2) among the most produced nanomaterials, has been documented in marine coastal areas posing a threat on marine biota. Sea urchin embryos are recognized as suitable bioindicators in ecological risk assessment and recently for nanomaterials. This study investigated the impact of nano-TiO2 on fertilization, embryonic and larval development of the tropical sea urchin Lytechinus variegatus in a range of concentrations (0.005-5 µg/mL) which includes environmentally relevant ones. The behavior of nano-TiO2 in tropical natural seawater was determined by dynamic light scattering (DLS) and toxicity was evaluated through fertilization and embryotoxicity tests, and morphological/morphometric analyses of sea urchin's larvae. Limited toxicity was recorded for nano-TiO2 in tropical sea urchin embryos and larvae, except for effects at the gastrula stage at 0.005 µg/mL. Large agglomerates of nano-TiO2 (5 µg/mL) were observed adhering onto sea urchin larvae thus probably preventing nanoparticles uptake at the highest concentrations (>0.005 µg/mL). Environmental levels of nano-TiO2 are able to cause toxicity on tropical sea urchin L. variegatus embryos with potential consequences on populations and their ecological role in tropical coastal areas.

Multifidus muscle cross-sectional area adaptations over two volleyball seasons and one off-season in athletes with and without low back pain.

BACKGROUND: The multifidus muscle is important in spine stabilization. Atrophy of the multifidus muscle has been associated with low back pain. OBJECTIVE: To examine multifidus muscle cross-sectional area (CSA) adaptations over two volleyball seasons and one off-season in volleyball athletes experiencing low back pain or no low back pain. METHODS: Twelve female NCAA division 1 volleyball athletes participated. Athletes were placed into a low back pain or no low back pain group. Athlete's multifidus was imaged and measured using ultrasound at four time points across seasons. Imaging time points were before season one, following season one, following off-season, and following season two. A single level mixed-model analysis of variance was used for all analyses. A Tukey HSD post hoc test was used to determine differences between and within the low back pain and the no low back pain groups. RESULTS: Following off-season training the pain group had clinically significant smaller multifidus CSA at the L4 (-2.36 cm2 difference or 17.5%) and L5 (-2.40 cm2 or 12.5%) levels. Non-significant (p> 0.05) decreases in multifidus CSA were seen in both groups following season one and two. Athletes with pain had decreased multifidus CSA at the L4 and L5 vertebral levels at all time points which was non-significant (p> 0.05). CONCLUSIONS: Clinically significant decreases in multifidus CSA occurred in female volleyball athletes with low back pain at the L4 and L5 level following off-season training. Volleyball athletes with pain had smaller multifidus CSA averages at all time points measured of the two year period.

Electrocardiography in Hypertensive Patients without Cardiovascular Events: A Valuable Predictor Tool?

Background: Hypertension is an important risk factor of cardiovascular (CV) disease. An early diagnosis of target organ damage could prevent major CV events. Electrocardiography (ECG) is a valuable clinical technique, with wide availability and high specificity, used in evaluation of hypertensive patients. However, the use of ECG as a predictor tool is controversial given its low sensitivity. This study aims to characterise ECG features in a hypertensive population and identify ECG abnormalities that could predict CV events. Methods: We studied 175 hypertensive patients without previous CV events during a follow-up mean of 4.0 ± 2.20 years. ECGs and pulse wave velocity were performed in all patients. Clinical characteristics and ECG abnormalities were evaluated and compared between the patients as they presented CV events. Results: Considering the 175 patients (53.14% male), the median age was 62 years. Median systolic blood pressure was 140 mmHg and diastolic blood pressure was 78 mmHg. Median PWV was 9.8 m/s. Of the patients, 39.4% were diabetic, 78.3% had hyperlipidaemia, and 16.0% had smoking habits. ECG identified left ventricular (LV) hypertrophy in 29.71% of the patients, and a LV strain pattern was present in 9.7% of the patients. Twenty-nine patients (16.57%) had a CV event. Comparative analyses showed statistical significance for the presence of a LV strain pattern in patients with CV events (p=0.01). Univariate and multivariate analysis confirmed that a LV strain pattern was an independent predictor of CV event (HR 2.66, 95% IC 1.01-7.00). In the survival analysis, the Kaplan-Meier curve showed a worse prognosis for CV events in patients with a LV strain pattern (p=0.014). Conclusion: ECG is a useful daily method to identify end-organ damage in hypertensive patients. In our study, we also observed that it may be a valuable tool for the prediction of CV events.

Guanine-induced inhibition of renal Na(+)-ATPase activity: evidence for the involvement of the Gi protein-coupled receptor.

There is some evidence to show a possible role of guanosine in the modulation of cellular function, in particular, in the neuronal system. However, nothing is known about the role of guanine in renal function. The aim of the present work was to investigate the role of guanine on modulation of Na+-ATPase activity in isolated basolateral membrane (BLM) of the renal cortex. Guanine inhibited the enzyme activity in a dose-dependent manner with maximal effect (56%) obtained at 10⁻6 M. This effect was reversed by DPCPX (8-cyclopentyl-1,3-dipropylxanthine), an antagonist of A1 receptors, but it was not changed by 10⁻8 M DMPX (3,7-dimethyl-1-propargylxanthine) or 10⁻8 M MRS (2,3-diethyl-4,5-dipropyl-6-phenylpyridine-3-thiocarboxylate-5-carboxylate), antagonists of A2 and A3 receptors, respectively. Furthermore, it was observed that guanine increased [γ-³5S]GTP-specific binding with the maximal effect observed at 10⁻6 M and this effect was abolished by 10⁻6 M GDPßS. The inhibitory effect of 10⁻6 M guanine on Na+-ATPase activity was reversed by 10⁻6 M GDPßS, 10⁻6 M forskolin, 10⁻6 M pertussis toxin and 10⁻8 M cholera toxin. These results indicate that guanine binds to a DPCPX-sensitive receptor promoting the activation of Gi protein and leading to a decrease in cAMP level and, consequently, inhibition of BLM Na+-ATPase activity.

Prostaglandin E2 modulates proximal tubule Na+-ATPase activity: cooperative effect between protein kinase A and protein kinase C.

Previous data showed that prostaglandin E2 (PGE2) mediates the inhibitory effect of bradykinin (BK) on proximal tubule (PT) Na+-ATPase activity. The aim of this work was to investigate the molecular mechanisms involved in the effect of PGE2 on PT Na+-ATPase. We used isolated basolateral membrane (BLM) from pig PT, which expresses several components of different signaling pathways. The inhibitory effect of PGE2 on PT Na+-ATPase activity involves G-protein and the activation of protein kinase A (PKA) because: (1) PGE2 increased [³5S]GTPγS binding; (2) GDPßS abolished the inhibitory effect of PGE2; (3) PGE2 increased PKA activity; (4) the inhibitory effect of PGE2 was abolished by PKA inhibitor peptide. We observed that the PKA-mediated inhibitory effect of PGE2 on PT Na+-ATPase activity requires previous activation of protein kinase C. In addition, we observed that PGE2 stimulates Ca²+-independent phospholipase A2 activity representing an important positive feedback to maintain the inhibition of the enzyme. These results open new perspectives to understanding the mechanism involved in the effect of PGE2 on proximal tubule sodium reabsorption.

Fully automated preoperative segmentation of temporal bone structures from clinical CT scans.

Middle- and inner-ear surgery is a vital treatment option in hearing loss, infections, and tumors of the lateral skull base. Segmentation of otologic structures from computed tomography (CT) has many potential applications for improving surgical planning but can be an arduous and time-consuming task. We propose an end-to-end solution for the automated segmentation of temporal bone CT using convolutional neural networks (CNN). Using 150 manually segmented CT scans, a comparison of 3 CNN models (AH-Net, U-Net, ResNet) was conducted to compare Dice coefficient, Hausdorff distance, and speed of segmentation of the inner ear, ossicles, facial nerve and sigmoid sinus. Using AH-Net, the Dice coefficient was 0.91 for the inner ear; 0.85 for the ossicles; 0.75 for the facial nerve; and 0.86 for the sigmoid sinus. The average Hausdorff distance was 0.25, 0.21, 0.24 and 0.45 mm, respectively. Blinded experts assessed the accuracy of both techniques, and there was no statistical difference between the ratings for the two methods (p = 0.93). Objective and subjective assessment confirm good correlation between automated segmentation of otologic structures and manual segmentation performed by a specialist. This end-to-end automated segmentation pipeline can help to advance the systematic application of augmented reality, simulation, and automation in otologic procedures.

Ecotoxicological effects of commercial herbicides on the reproductive system of aquatic arthropod Limnocoris submontandoni (Hemiptera: Naucoridae).

Worldwide, conventional agriculture makes extensive use of pesticides. Although the effects of herbicides are relatively well known in terms of environmental impacts on non-target organisms, there is very little scientific evidence regarding the impacts of herbicide residues on aquatic arthropods from tropical conservation areas. This study evaluates for the first time the toxicity of the herbicides ametryn, atrazine, and clomazone on the aquatic insect Limnocoris submontandoni (Hemiptera: Naucoridae). The lethal concentration (LC50) of herbicides was evaluated for these insects, as well as the effect of the herbicides on the insects' tissues and testicles. The estimated LC50 was 1012.41, 192.42, and 46.09 mg/L for clomazone, atrazine, and ametryn, respectively. Spermatocyte and spermatid changes were observed under the effect of atrazine, and effects on spermatogenesis were observed for some concentrations of clomazone, with apparent recovery after a short time. Our results provide useful information on the effects of herbicide residues in aquatic systems. This information can help minimize the risk of long-term reproductive effects in non-target species that have been previously overlooked in ecotoxicology studies.

Association of positive and negative life events with cognitive performance and psychological status in late life: A cross-sectional study in Northern Portugal.

Objectives: Life events have important effects on psychological well-being. Yet, studies have mainly focused on exploring the impact of traumatic and negative experiences on health and well-being, with positive events receiving marginal attention. In this study, we investigated the association between negative and positive life events, cognitive performance and psychological status in older individuals. Method: A cross-sectional approach with a sample of 97 community-dwelling adults, recruited from a network of 23 centres/institutions in Northern Portugal, and aged between 56 and 85 years, was conducted. All participants were evaluated through a battery of tests assessing for depressive mood, perceived stress, and cognitive functioning. Life events were measured using the Lifetime Experiences Scale (LIFES) which covers 75 life experiences organized in eight domains. Results: A total of 95.9% of the participants reported more positive life events than negative throughout life. Participants reporting more positive experiences had lower scores in the depressive mood and perceived stress measures. At the domain-level of LIFES scale, more negative experiences in the Work and Health domains were associated with a depressed mood and more perceived stress. Significant positive associations were found between positive life experiences and most cognitive measures, after controlling for sex, education, age and depressive symptoms. Namely, more positive experiences at School, Leisure, and Living conditions were positively associated with better performance across cognitive tests. Discussion: This study adds important evidence on the association between of life events, both negative and positive experiences, on cognition and psychological well-being, providing a more balanced view of the field.

Cardiolipin, a key component to mimic the E. coli bacterial membrane in model systems revealed by dynamic light scattering and steady-state fluorescence anisotropy.

The phase transition temperatures of several lipidic systems were determined using two different techniques: dynamic light scattering (DLS) and steady-state fluorescence anisotropy, using two fluorescent probes that report different membrane regions (TMA-DPH and DPH). Atomic force microscopy (AFM) was used as a complementary technique to characterize different lipid model systems under study. The systems were chosen due to the increased interest in bacterial membrane studies due to the problem of antibiotic drug resistance. The simpler models studied comprised of mixtures of POPE and POPG lipids, which form a commonly used model system for Escherichia coli membranes. Given the important role of cardiolipin (CL) in natural membranes, a ternary model system, POPE/POPG/CL, was then considered. The results obtained in these mimetic systems were compared with those obtained for the natural systems E. coli polar and total lipid extract. DLS and fluorescence anisotropy are not commonly used to study lipid phase transitions, but it was shown that they can give useful information about the thermotropic behaviors of model systems for bacterial membranes. These two techniques provided very similar results, validating their use as methods to measure phase transitions in lipid model systems. The temperature transitions obtained from these two very different techniques and the AFM results clearly show that cardiolipin is a fundamental component to mimic bacteria membranes. The results suggest that the less commonly used ternary system is a considerably better mimic for natural E. coli membranes than binary lipid mixture.

L-arginine and L-nitroarginine methylester effects on vasomotion in isolated rabbit eyes.

BACKGROUND/AIMS: Although nitric oxide (NO) has been shown to be essential for maintaining the basal blood flow in the retina and optic nerve head, its exact role in vasomotion is still controversial. This study investigated L-arginine (L-Arg) and N-nitro-L-arginine methylester (L-NAME) effects on vascular reactivity in a model of isolated rabbit eye. METHODS: Rabbit external ophthalmic arteries (n = 12) in a head-mounted preparation were cannulated and perfused with warmed Tyrode solution. The effect of intraluminal pressure as a measure of total vascular resistance was assessed. Response curves to intra-arterial injections of 3 growing concentrations of L-Arg (n = 6) and L-NAME (n = 6) were obtained. RESULTS: Without any drug administration, spontaneous oscillations were observed in all the models. L-Arg (NO precursor) induced vasodilation and decreased both frequency and amplitude of the periodic oscillations. L-NAME (NO synthase inhibitor) produced a strong vasoconstrictor tone and stimulated vasomotion, causing a faster rate of pulsatility. CONCLUSION: L-Arg and L-NAME acted as modulators of ocular vascular tone. L-Arg elicited vasodilation and decreased vasomotion while L-NAME produced a strong vasoconstrictor tone and caused a faster rate of pulsatility. These findings justify the need to investigate NO precursors and antagonists as possible alternative therapeutics in vascular eye diseases.

Incorporation of tocopherol acetate-containing particles in acrylic bone cement.

Acrylic bone cement (BC) is used in orthopaedic surgery to anchor cemented prostheses to bone. Association of antioxidant molecules to BC may suppress reactive species injury which contributes to implant failure. Tocopherol acetate (ATA)-loaded polymethylmethacrylate (PMMA) particles (ATA(PMMA)) were prepared by single emulsion solvent evaporation technique and were incorporated into BC. An encapsulation efficiency of 84% (w/w) was obtained and drug release studies showed distinct ATA release profiles and mechanisms before and after particle incorporation into BC. Experimental data, analysed using first-order, Higuchi and Korsmeyer-Peppas models revealed that ATA was released from particles by a Fickian diffusion mechanism while a non-Fickian transport was observed upon particle incorporation in BC. There were no changes in the mechanical properties of BC specimens containing ATA(PMMA) particles, in contrast to what was observed when ATA was loaded directly into BC. Overall, ATA(PMMA) particles are potential carriers for the incorporation of an antioxidant drug into BC.

Standardization of antimicrobial testing of dental devices.

OBJECTIVE: Dental device is a very broad term that can be used to include any foreign material or product that is introduced in the host oral cavity to replace missing tissues. These devices are subjected to different environments which include dental hard tissues, tissue fluids, blood and saliva. All dental devices are continuously challenged microbiologically and a number of failures in clinical management are related to microbial colonization. Thus, the assessment of the antimicrobial properties of dental devices are extremely important. In this paper, a classification of dental devices is being proposed. This classification distinguishes the devices based on whether they are implantable or not, and also sub-classified based on their specific application and the substrate receiving the device. METHODS AND RESULTS: A literature search was conducted to identify how dental devices have been tested with relation to the microbial strains used and whether the testing has been performed in isolation or reported with other relevant tests such as material characterization and biological activity. The results of the literature review were analyzed and recommendations for antimicrobial testing of dental devices are proposed. These recommendations include the need for the setting up of pre-testing parameters such as ageing and the details of the pre-testing sterilization procedures, as these may affect the material chemistry and the specification for antimicrobial testing to be done with specific single strains or polymicrobial that are native to the region where the device is located are also suggested. Testing can be undertaken in vitro, ex vivo and in vivo. Since the antimicrobial and biological activities influence/condition one another and the material chemistry may affect both the antimicrobial and biological testing this document also makes recommendations regarding biological assessment which can be carried out in isolation or integrated with the microbiological testing and also material testing methods including chemical and physical characterization of bulk, surface, eluted and degraded materials as well as physical characterization methods. SIGNIFICANCE: The level of standardization of antimicrobial testing for the dental devices needs to be based on the device location and host interaction in order to increase the clinical applicability of the mentioned tests.